• Journal of Microbiology and Biotechnology
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• 제34권10호
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• pp.1995-2004
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• 2024

Gut microbial metabolites have been demonstrated to play a role in diabetes mellitus and gestational diabetes mellitus (GDM). This study aimed to investigate gut microbiome, fecal metabolomics, and their association in pregnant women with and without GDM. The metabolome indicated that the top 2 differential metabolic pathways between control (Con) and GDM groups were phenylalanine metabolism and nucleotide metabolism. The increased Phenylalanylglycine, m-coumaric acid, and Phenylacetic acid were among the top differential metabolites between Con and GDM groups and involved in phenylalanine metabolism. Uracil and hypoxanthine were top differential metabolites in Con vs. GDM and involved in nucleotide metabolism. The proficiently altered gut microbiota at the class level was c_unclassified_ Firmicutes. Association analysis between gut microbiota and fecal metabolites indicated that the increased gut symbiont Clostridium belonged to Firmicutes and was linked to the dysregulation of phenylalanine metabolism in GDM. This study may provide the mechanism underlying how Clostridium-phenylalanine metabolism association contributes to GDM pathogenesis and also be a novel therapeutic strategy to treat GDM.

• Asian-Australasian Journal of Animal Sciences
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• 제33권11호
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• pp.1770-1778
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• 2020

Objective: This study was conducted to reveal potential metabolic differences of dairy cows fed corn stover (CS) and rice straw (RS) instead of alfalfa hay (AH) as main forage source. Methods: Thirty multiparous mid-late lactation Holstein dairy cows were selected and randomly assigned to three diets, AH, CS, or RS (n = 10). After 13 weeks of the feeding trial, coccygeal arterial and superficial epigastric venous plasma samples were collected before morning feeding for gas chromatography time-of-flight/mass spectrometry analyses. Results: In the artery, 8 and 13 metabolites were detected as differential metabolites between AH and CS, and between AH and RS, respectively. The relative abundance of phenylpropanoate (log₂fold change [FC]) = 1.30, 1.09), panthenol (log₂FC = 2.36, 2.20), threitol (log₂FC = 1.00, 1.07), and 3,7,12-trihydroxycoprostane (log₂FC = 0.79, 0.78) were greater in both CS and RS than in AH, and tyrosine (log₂FC = -0.32), phenylalanine (log₂FC = -0.30), and pyruvic acid (log₂FC = -0.30) were lower in RS than in AH. In the vein, 1 and 7 metabolites were detected as differential metabolites between AH and CS, and between AH and RS, respectively. By comparing AH and RS, we found that metabolic pathways of phenylalanine, tyrosine, and tryptophan biosynthesis and phenylalanine metabolism were enriched by integrative artery and vein analysis. Furthermore, AH and RS, arterial phenylpropanoate and 4-hydroxyproline were positively, and phenylalanine was negatively correlated with milk urea nitrogen. Finally, in AH and CS, arterial panthenol was negatively correlated with feed efficiency. Conclusion: Arterial metabolic profiles changed more than those in the veins from animals on three forage diets, differing in amino acids. We found that phenylalanine, tyrosine, and tryptophan biosynthesis and phenylalanine metabolism were restricted when cows were fed low-quality cereal straw diets.

• Mycobiology
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• 제39권4호
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• pp.257-265
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• 2011

L-Phenylalanine is one of the essential amino acids that cannot be synthesized in mammals in adequate amounts to meet the requirements for protein synthesis. Fungi and plants are able to synthesize phenylalanine via the shikimic acid pathway. L-Phenylalanine, derived from the shikimic acid pathway, is used directly for protein synthesis in plants or metabolized through the phenylpropanoid pathway. This phenylpropanoid metabolism leads to the biosynthesis of a wide array of phenylpropanoid secondary products. The first step in this metabolic sequence involves the action of phenylalanine ammonialyase (PAL). The discovery of PAL enzyme in fungi and the detection of $^{14}CO_2$ production from $^{14}C$-ring-labeled phenylalanine and cinnamic acid demonstrated that certain fungi can degrade phenylalanine by a pathway involving an initial deamination to cinnamic acid, as happens in plants. In this review, we provide background information on PAL and a recent update on the presence of PAL genes in fungi.

• 한국균학회지
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• 제39권3호
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• pp.249-253
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• 2011

Ustilago maydis(옥수수깜부기균)에 있어서 동포자 melanin의 구성성분으로 catecol 계 알려진바 이 물질의 전구체인 benzoic acid의 생성 여부와 그 유래 원천을 추적하고자 phenylalanine의 분해 과정을 조사하였다. 방사성 동위원소가 표지된 L-$^{14}C$-phenylalanine 및 $^{14}C$-trans-cinnamic acid를 첨가한 액체배지에서 균체와 배양액을 대상으로 대사산물을 추적 조사한 결과 trans-cinnamic acid, benzoic acid, 4-hydroxybenzoic acid와 hydroxybenzoic acid derivatives 추정되는 물질 등이 검출되었다. 또한 L-$^{14}C$-phenylalanine을 대사하여 매우 천천히 공기 중으로 $^{14}CO_2$를 방출함을 확인하여 phenylalanine을 완전히 분해 할 수 있음을 밝혔다. 결론적으로 본 연구는 옥수수깜부기균이 benzoic acid를 생성하고 그 유래는 phenylalanine의 분해에서 만들어지는 증거를 제시하였다.

• Asian-Australasian Journal of Animal Sciences
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• 제20권4호
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• pp.536-542
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• 2007

The responses of whole body protein and glucose kinetics and of nitrogen (N) metabolism to non-protein energy intake (NPEI) were determined using an isotope dilution approach and measurement of N balance in three adult male goats. The diets containing 1.0, 1.5 and 2.0 times ME maintenance requirement, with fixed intake of CP (1.5 times maintenance) and percentage of hay (33%), were fed twice daily for each 21 d experimental period. After an adaptation period of 11 d, N balance was determined over 3 d. On day 17, whole body protein synthesis (WBPS) and glucose irreversible loss rate (ILR) were determined during the absorptive state by a primed-continuous infusion of [$^2H_5$]phenylalanine, [$^2H_2$]tyrosine, [$^2H_4$]tyrosine and [$^{13}C_6$]glucose, with simultaneous measurements of plasma concentrations of metabolites and insulin. Ruminal characteristics were also measured at 6 h after feeding over 3 d. Nitrogen retention tended to increase (p<0.10) with increasing NPEI, although digestible N decreased linearly (p<0.05). Increasing NPEI decreased (p<0.01) ammonia N concentration, but increased acetate (p<0.05) and propionate (p<0.05) concentrations in the rumen. Despite decreased plasma urea N concentration (p<0.01), increased plasma tyrosine concentration (p<0.05), and trends toward increased plasma total amino N (p<0.10) and phenylalanine concentrations (p<0.10) were found in response to increasing NPEI. Increasing NPEI increased ILR of both glucose (p<0.01) and phenylalanine (p<0.05), but did not affect ($p{\geq}0.10$) that of tyrosine. Whole body protein synthesis increased (p<0.05) in response to increasing NPEI, resulting from increased utilization rate for protein synthesis (p<0.05) and unchanged hydroxylation rate of phenylalanine ($p{\geq}0.10$). These results suggest that increasing NPEI may enhance WBPS and glucose turnover at the absorptive state and improve the efficiency of digestible N retention in goats, with possibly decreased ammonia and increased amino acid absorption. In addition, simultaneous increases in WBPS and glucose ILR suggest stimulatory effect of glucose availability on WBPS, especially when sufficient amino acid is supplied.

• Journal of Microbiology and Biotechnology
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• 제20권3호
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• pp.622-629
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• 2010

Biosynthetic studies on brasiliamides, potently convulsive and bacteriostatic compounds from an endophytic Penicillium brasilianum isolated from Melia azedarach (Meliaceae), confirms their phenylpropanoid origin, which is very uncommon in fungi. Feeding experiments with [$2-^{13}C$]-phenylalanine indicated the incorporation of two units of this amino acid on brasiliamide structures. The first step in the phenylpropanoid pathway to those compounds was evaluated through enzymatic bioassays and confirmed the phenylalanine ammonia-lyase (PAL) participation. The metabolism of phenylalanine in this fungus is discussed.

• 대한유전성대사질환학회지
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• 제20권2호
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• pp.37-43
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• 2020

페닐케톤뇨증(PKU)은 전세계적으로 가장 잘 알려지고 중요한 유전성 대사질환이다. 1950년대 이후 단백제한을 이용한 식사치료를 처음으로 시도하여 성과가 있었던 질환이며 1960년대 이후 신생아선별검사를 통해 조기진단과 조기치료가 가능하게 된 최초의 유전성대사질환이기 때문이다. 단백제한 식사치료의 효과가 좋지만 학동기, 사춘기 이후 성인시기까지 유지하는 것의 어려움이 있고 이시기에 조절이 잘 되지 않았을 경우 경련, 여러가지 정신과적인 문제들, 삶의 질의 감소 등이 문제가 되어서 오랜 기간 치료를 위한 여러 방법들이 제시되었다. 더해서 2014년 미국의학유전학회(American Medical College of Medical Genetics and Genomics, ACMG)에서 전 연령에서 혈중 페닐알라닌 수치를 120-360 umol/L로 제시를 한 이후 더욱 치료의 중요성이 올라갔다. 2000년대 페닐알라닌수산화 효소(phenylalanine hydroxylase, PAH)의 조효소인 tetrahydrobiopterin (BH4)가 치료 승인되어서 약물반응을 보이는 환자에서 치료가 시작되었으며 4세미만에서도 허가가 되어서 이른 시기부터 약물치료를 병행하여 효과를 보게 되었다. 높은 혈중 페닐알라닌수치가 혈액-뇌 장벽(Blood-brain barrier, BBB)을 통하여 뇌로 넘어가서 회백질의 변성을 나타내게 되는 문제를 막기 위해 거대중성아미노산(LNAA)를 이용한 치료가 시도되고 있다. 오랫동안 연구되었던 페닐알라닌을 trans-cinnamic acid와 암모니아로 변화를 시키는 phenylalanine ammonialyase (PAL)을 이용한 효소치료는 최근 약제로 개발되어서 2018년 이후 성인환자를 대상으로 치료가 시작되었고 잘 조절되지 않는 환자들에게 효과를 보이고 있다. PAL을 경구용으로 개발하는 것이 빠르게 진행 중이며 유전자치료에 대한 연구들도 활발하게 진행이 되고 있어 다양한 치료들이 앞으로 기대된다.

• Animal Bioscience
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• 제36권2호
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• pp.229-237
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• 2023

Objective: This study evaluated the effects of dandelion supplements on lactation performance, circulating antioxidative activity and plasma metabolomics in primiparous dairy cows. Methods: A total of 60 mid-lactation dairy cows (milk yield = 34.29±0.34 kg/d; days in milk = 151.72±2.36 days) were divided into 4 treatment groups randomly, comprising the addition of dandelion at 0, 100, 200, 400 g/d per head. The experiment lasted for 8 weeks with an extra 10 days' pre-feeding period. Milk and blood samples were collected, and plasma samples were selected to perform metabolomics analysis. Results: Supplementing 200 g/d of dandelion increased the yield of milk and lactose (p≤0.05). The milk somatic cell counts (p≤0.05) were lower in all dandelion groups than those in the control group. The activity of glutathione peroxidase (p≤0.05) and superoxide dismutase (p≤0.05) were increased and plasma malondialdehyde (p = 0.01) was decreased when cows were fed 200 g/d dandelion. Plasma metabolomics analysis showed that 23 hub differential metabolites were identified in the 200 g/d dandelion group. These metabolites such as ribose, glutamic acid, valine, and phenylalanine were enriched in D-glutamine and D-glutamate metabolism (p = 0.06, impact value = 1), phenylalanine, tyrosine, and tryptophan biosynthesis (p = 0.05, impact value = 0.5), and starch and sucrose metabolism (p = 0.21, impact value = 0.13). Moreover, correlation analysis showed that circulating ribose, mannose, and glutamic acid were positively related to milk yield. Conclusion: Dandelion supplementation could improve lactation performance and elevate the plasma carbohydrate and amino acids metabolism and antioxidative activity. Supplementation of 200 g/d dandelion is recommended for lactating dairy cows.

• Journal of Nutrition and Health
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• 제4권4호
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• pp.39-46
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• 1971

Iso-butyl bromide의 합성을 시작으로 D.L-1-amino-3-methylbutylphosphonic acid의 합성을, Diethyl phophite의 합성을 시작으로 D.L-1-amino-2-phenyl ethylphosphonic acid의 합성을 하였다. 합성되어진 필수 아미노산인 Isoleucine analogue phosphonic acid는 각각 0.2%, 0.4%를 식이에 첨가했고 Phenylalanine analogue phosphonic acid는 0.35%와 0.7%를 각각 첨가하였으며 Standard-1과 Standard-2군과 비교군인 Isoleucine 0.2%와 0.4% Phenylalanine 0.35%와 0.7%군으로써 총 100마리의 숫쥐로 각 7주씩 14주의 사육 실험을 하였다. 동물 사육 기간내의 뇨채취와 사육후의 각 장기의 채취로써 총 질소와 P, glycogen측정을 시도하였다. 이러한 일련의 실험결과 (1) D.L-1-amino-3-methylbuthylphosphonic acid나D.L-1-amino-2-phenylethylphosphonic acid의 유기 합성에 있어서는 다 수율이 낮고 상당히 높은 융점을 보였으며 ${\alpha}-NH_2$기가 Ninhydrin 반응에 예민했다. (2) Aminophosphonic acid의 첨가군(D.L-1-amino-3-methylbutyl phosphonic acid, D.L-1-amino-2-Phenylethylphosphonic acid)에서나 Amino acid(Isoleucine, Phenylalanine)첨가군에 있어서 모든 장기의 무게, 총체내질소 보유율, 간장내 총단백질량과 인의양, 및 뇨를 통한 인의 배설량에 각각 큰 차이를 보이지 않았다. 이로 보아서 Phenylalanine Aminophosphonic acid나 Isoleucine aminophosphonic acid가 다 보통 아미노산인 Isoleucine이나 Phenylalanine에 못지않게 체내에서 이용됨이 밝혀졌다. (3) 그러나 Phenylalanine aminophosphonic acid 첨가군이 간의 glycogen 함량에 있어서 Phenylalanine 첨가군과 Standard군과 비교해 보았을때 높았으며 이는 통계적인 유의성을 나타냈다.(<0.05) 이는 Phenylalanine Aminophosphonic Acid가 active state로써 간내에서 쉽게 이용되어서 Tricarboxylic cycle의 intermediate로 incorporate되는 경향으로 생각 할 수 있다.

• 한국식품영양과학회지
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• 제14권1호
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• pp.27-32
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• 1985

화분립이 alcohol대사에 미치는 영향을 알기 위하여 아미노산을 분석하고, rat에 alcohol과 화분립을 각각 농도별로 투여하여 rat 간(肝) alcoholdehydrogenase (ADH)활성과 간(肝)조직 변화를 실험하였다. 1. 해바라기 화분립의 아미노산 조성을 분석하여 phenylalanine을 비롯한 18종의 아미노산을 정량하였으며, 필수 아미노산중 특히 phenylalanine, leucine, threonine, lysine의 함량이 많았다. 2. 실험동물의 간(肝) ADH활성은 alcohol 투여군이 alcohol농도에 비례하여 대조군 보다 현저히 저하하였으며, 화분립을 alcohol과 함께 투여함으로써, 대조군에는 미치지 않았지만 ADH활성이 증가하였고, alcohol의 농도가 낮을수록 그 증가율이 높았다. 3. 실험동물의 간(肝)조직은 alcohol투여군에서 지방침윤이 나타났으며, 화분립과 alcohol 복합투여군에서는 지방침윤이 현저히 적게 나타났다.